The number of individuals affected by diabetes mellitus is rising at epidemic proportions, particularly in the Latino population of the United States. Diabetic retinopathy is one of most devastating complications of diabetes and is the leading cause of blindness in working age Americans. Even after accounting for other risk factors, such as blood sugar levels, Latinos appear to have higher rates of diabetic retinopathy compared with other ethnic groups. A National Eye Institute-funded study of Latino adults in Los Angeles revealed that nearly half of all Latino diabetics had evidence of diabetic retinopathy. Genetic factors have been suggested to play a role in the development of diabetes and diabetic retinopathy and may explain the apparent increased risk of developing these problems in the Latino population. We have hypothesized that identification of alleles with the strongest effect may be facilitated by studying patients with the most severe phenotypes or advanced complications of diabetes. In the present research program we propose to identify genetic risk factors for diabetic retinopathy by focusing on the Latino population in southern California who are affected by a severe diabetic microvascular complication, proliferative diabetic retinopathy (PDR). Our goal will be to recruit a large cohort of carefully phenotyped cases and controls which can be evaluated in subsequent genome wide association studies to identify genetic variants that predispose individuals to develop PDR.